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Nucleic Acids Research, 1993, Vol. 21, No. 19 4530-4540
© 1993

COMPUTATIONAL BIOLOGY

An adaptive, object oriented strategy for base calling in DNA sequence analysis

Michael C. Giddings, Robert L. Brumley, Jr, Michael Haker and Lloyd M. Smith*

Chemistry Department, University of Wisconsin 1101 University Avenue,Madison, Wl 53706, USA

*To whom correspondence should be addressed

Received June 18, 1993. Revised August 18, 1993. Accepted August 18, 1993.

An algorithm has been developed for the determination of nucleotide sequence from data produced in fluorescence-based automated DNA sequencing instruments employing the four-color strategy. This algorithm takes advantage of object oriented programming techniques for modularity and extensibility. The algorithm is adaptive in that data sets from a wide variety of instruments and sequencing conditions can be used with good results. Confidence values are provided on the base calls as an estimate of accuracy. The algorithm iteratively employs confidence determinations from several different modules, each of which examines a different feature of the data for accurate peak identification. Modules within this system can be added or removed for increased performance or for application to a different task. In comparisons with commercial software, the algorithm performed well.


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